Small molecules which affect the tubulin polymerization have attracted much attention in chemistry, biology, and particularly in medicine fields for the past few years. One of the recognized targets in cancer research is represented by microtubules (Tubulin as a Target for Anticancer Drugs: Agents which Interact with the Mitotic Spindle. Jordan, A.; Hadfield, J. A.; Lawrence, N. J.; McGown, A. T. Med. Res. Rev. 1998, 18, 259-296.). Microtubule-targeting agents (taxanes and vinca alkaloids) have played a crucial role in the treatment of diverse human cancers (Microtubules as a Target for Anticancer Drugs. Jordan, M. A.; Wilson, L. Nat. Rev. Cancer 2004, 4, 253-265). However, they have certain limitations in their clinical utility, such as drug resistance, high systemic toxicity, complex syntheses, and isolation procedure. Therefore, identification of new molecules with tubulin binding mechanism is attractive for the discovery and development of novel anticancer agents.
E7010, (Novel sulfonamides as potential, systemically active antitumor agents. Yoshino, H.; Ueda, N.; Niijima, J.; Sugumi, H.; Kotake, Y.; Koyanagi, N.; Yoshimatsu, K.; Asada, M.; Watanabe, T.; Nagasu, T. J. Med. Chem. 1992, 35, 2496-2497) a sulphonamide exhibits good antitumor activity by inhibiting tubulin polymerization, (In vivo tumor growth inhibition produced by a novel sulfonamide, E7010, against rodent and human tumors Koyanagi, N.; Nagasu, T.; Fujita, F.; Watanabe, T.; Tsukahara, K.; Funahashi, Y.; Fujita, M.; Taguchi, Yoshino, H.; Kitoh, K. Cancer Res. 1994, 54, 1702-1706.), which causes cell cycle arrest and apoptosis in M phase (Yokoi, A.; Kuromitsu, J.; Kawai, T.; Nagasu, T.; Sugi, N. H.; Yoshimatsu, K.; Yoshino, H.; Owa, T. Mol. Cancer. Ther. 2002, 1, 275-286; Mechanism of action of E7010, an orally active sulfonamide antitumor agent: inhibition of mitosis by binding to the colchicine site of tubulin. Yoshimatsu, K.; Yamaguchi, A.; Yoshino, H.; Koyanagi, N.; Kitoh, K. Cancer Res. 1997, 57, 3208-3213.).
1,2,3-triazole moieties have displayed a broad range of biological properties such as antifungal, anti-allergic, antibacterial, anti-HIV, anticonvulsant, anti-inflammatory and antitubercular activities. Particularly, these triazoles exhibited anticancer activity (Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers. Kamal, A.; Prabhakar, S.; Ramaiah, M. J.; Reddy, P. V.; Reddy, C. R.; Mallareddy, A.; Shankaraiah, N.; Reddy, T. L. N.; Pushpavalli, S. N. C. V. L.; Bhadra, M. P. Eur. J. Med. Chem. 2011, 46, 3820-3831; Stefely et al. have described a limited number of 1,3-oxazole triazoles which have a limited scope of determining the antitumor activity of these of these compounds. N-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide as a new scaffold that provides rapid access to antimicrotubule agents: Synthesis and evaluation of antiproliferative activity against select cancer cell Lines. Stefely, J. A.; Palchaudhuri, R.; Miller, P. A.; Peterson, R. J.; Moraski, G. C.; Hergenrother, P. J.; Miller, M. J. J. Med. Chem. 2010, 53, 3389-3395). Accordingly, there is a need of more potent antitumor agents which is solved by the present invention.